@article{4f308fc0dcc7470681598937903d6b21,
title = "Relationships between rectal and perirectal doses and rectal bleeding or tenesmus in pooled voxel-based analysis of 3 randomised phase III trials",
abstract = "Background and purpose: This study aimed to identify anatomically-localised regions where planned radiotherapy dose is associated with gastrointestinal toxicities in healthy tissues throughout the pelvic anatomy. Materials and methods: Planned dose distributions for up to 657 patients of the Trans Tasman Radiation Oncology Group 03.04 RADAR trial were deformably registered onto a single exemplar computed tomography dataset. Voxel-based multiple comparison permutation dose difference testing, Cox regression modelling and LASSO feature selection were used to identify regions where dose-increase was associated with grade ≥2 rectal bleeding (RB) or tenesmus, according to the LENT/SOMA scale. This was externally validated by registering dose distributions from the RT01 (n = 388) and CHHiP (n = 241) trials onto the same exemplar and repeating the tests on each of these data sets, and on all three datasets combined. Results: Voxel-based Cox regression and permutation dose difference testing revealed regions where increased dose was correlated with gastrointestinal toxicity. Grade ≥2 RB was associated with posteriorly extended lateral beams that manifested high doses (>55 Gy) in a small rectal volume adjacent to the clinical target volume. A correlation was found between grade ≥2 tenesmus and increased low-intermediate dose (∼25 Gy) at the posterior beam region, including the posterior rectum and perirectal fat space (PRFS). Conclusions: The serial response of the rectum with respect to RB has been demonstrated in patients with posteriorly extended lateral beams. Similarly, the parallel response of the PRFS with respect to tenesmus has been demonstrated in patients treated with the posterior beam.",
keywords = "Bleeding, EBRT, Prostate, Tenesmus, Toxicity, Voxels",
author = "Marco Marcello and Denham, {James W.} and Angel Kennedy and Annette Haworth and Allison Steigler and Greer, {Peter B.} and Holloway, {Lois C.} and Dowling, {Jason A.} and Jameson, {Michael G.} and Dale Roach and Joseph, {David J.} and Gulliford, {Sarah L.} and Dearnaley, {David P.} and Sydes, {Mathew R.} and Emma Hall and Ebert, {Martin A.}",
note = "Funding Information: We acknowledge funding from the Australian National Health and Medical Research Council (grants 300705 , 455521 , 1006447 , 1077788 ), the Hunter Medical Research Institute , the Health Research Council (New Zealand), the University of Newcastle , the Calvary Mater Newcastle , the Medical Research Council Clinical Trials Unit at University College London, Abbott Laboratories and Novartis Pharmaceuticals . We acknowledge funding form the Medical Research Council UK (grant MC_UU_12023/28 ) for the MRC RT01 trial. David Dearnaley, Emma Hall and Sarah Gulliford acknowledge NHS funding to the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research , London. We acknowledge support of Cancer Research UK ( C8262/A7253 , C1491/A9895 , C1491/A15955 , SP2312/021 ), the Department of Health, the NIHR Cancer Research Network for the CHHiP trial. We acknowledge all trial investigators and patients who{\textquoteright}ve made this study possible. We gratefully acknowledge the support of the Sir Charles Gairdner Hospital, Rachel Kearvell, the {\textquoteleft}Elvis{\textquoteright} study team including Kristie Harrison, participating RADAR centres, the Trans Tasman Radiation Oncology Group, Ben Hooton and Elizabeth van der Wath. We are also grateful for the contributions of Oscar Acosta, Renaud de Crevoisier, and Eugenia Mylona. Funding Information: We acknowledge funding from the Australian National Health and Medical Research Council (grants 300705, 455521, 1006447, 1077788), the Hunter Medical Research Institute, the Health Research Council (New Zealand), the University of Newcastle, the Calvary Mater Newcastle, the Medical Research Council Clinical Trials Unit at University College London, Abbott Laboratories and Novartis Pharmaceuticals. We acknowledge funding form the Medical Research Council UK (grant MC_UU_12023/28) for the MRC RT01 trial. David Dearnaley, Emma Hall and Sarah Gulliford acknowledge NHS funding to the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London. We acknowledge support of Cancer Research UK (C8262/A7253, C1491/A9895, C1491/A15955, SP2312/021), the Department of Health, the NIHR Cancer Research Network for the CHHiP trial. We acknowledge all trial investigators and patients who've made this study possible. We gratefully acknowledge the support of the Sir Charles Gairdner Hospital, Rachel Kearvell, the ?Elvis? study team including Kristie Harrison, participating RADAR centres, the Trans Tasman Radiation Oncology Group, Ben Hooton and Elizabeth van der Wath. We are also grateful for the contributions of Oscar Acosta, Renaud de Crevoisier, and Eugenia Mylona. Funding Information: Mr Sydes reports grants from Health Data Research UK, during the conduct of the study; personal fees from Lilly Oncology, personal fees from Janssen, grants and non-financial support from Astellas, grants and non-financial support from Clovis Oncology, grants and non-financial support from Janssen, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Sanofi-Aventis, outside the submitted work. Publisher Copyright: {\textcopyright} 2020 Funding Information: We acknowledge funding from the Australian National Health and Medical Research Council (grants 300705 , 455521 , 1006447 , 1077788 ), the Hunter Medical Research Institute , the Health Research Council (New Zealand), the University of Newcastle , the Calvary Mater Newcastle , the Medical Research Council Clinical Trials Unit at University College London, Abbott Laboratories and Novartis Pharmaceuticals . We acknowledge funding form the Medical Research Council UK (grant MC_UU_12023/28 ) for the MRC RT01 trial. David Dearnaley, Emma Hall and Sarah Gulliford acknowledge NHS funding to the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research , London. We acknowledge support of Cancer Research UK ( C8262/A7253 , C1491/A9895 , C1491/A15955 , SP2312/021 ), the Department of Health, the NIHR Cancer Research Network for the CHHiP trial. We acknowledge all trial investigators and patients who{\textquoteright}ve made this study possible. We gratefully acknowledge the support of the Sir Charles Gairdner Hospital, Rachel Kearvell, the {\textquoteleft}Elvis{\textquoteright} study team including Kristie Harrison, participating RADAR centres, the Trans Tasman Radiation Oncology Group, Ben Hooton and Elizabeth van der Wath. We are also grateful for the contributions of Oscar Acosta, Renaud de Crevoisier, and Eugenia Mylona. Funding Information: We acknowledge funding from the Australian National Health and Medical Research Council (grants 300705, 455521, 1006447, 1077788), the Hunter Medical Research Institute, the Health Research Council (New Zealand), the University of Newcastle, the Calvary Mater Newcastle, the Medical Research Council Clinical Trials Unit at University College London, Abbott Laboratories and Novartis Pharmaceuticals. We acknowledge funding form the Medical Research Council UK (grant MC_UU_12023/28) for the MRC RT01 trial. David Dearnaley, Emma Hall and Sarah Gulliford acknowledge NHS funding to the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London. We acknowledge support of Cancer Research UK (C8262/A7253, C1491/A9895, C1491/A15955, SP2312/021), the Department of Health, the NIHR Cancer Research Network for the CHHiP trial. We acknowledge all trial investigators and patients who've made this study possible. We gratefully acknowledge the support of the Sir Charles Gairdner Hospital, Rachel Kearvell, the ?Elvis? study team including Kristie Harrison, participating RADAR centres, the Trans Tasman Radiation Oncology Group, Ben Hooton and Elizabeth van der Wath. We are also grateful for the contributions of Oscar Acosta, Renaud de Crevoisier, and Eugenia Mylona. Publisher Copyright: {\textcopyright} 2020",
year = "2020",
month = sep,
doi = "10.1016/j.radonc.2020.07.048",
language = "English",
volume = "150",
pages = "281--292",
journal = "Radiotherapy and Oncology",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",
}